Hindlimb unweighing (HU) is a model used to simulate select condition of microgravity. Rats exposed to HU exhibit reductions in exercise capacity characterized by lower measures of maximal oxygen uptake (VO2 max). The mechanism for this deconditioning effect involves an impaired ability to increase skeletal muscle blood flow during exercise. The general aim of this study is to determine whether endothelium-dependent vasodilator responses are impaired in HU rats. In addition we will determine whether HU causes a decrease in vascular flow capacity and the potential for capillary exchange in the hindlimbs. Five specific aims will be addressed. Aim #1 will determine the effects of HU on the potential for endothelium- dependent vasodilation in a conduit artery and microvascular resistance arteries isolated from the plantaris and soleus muscles. Aim #2 will determine the effect of HU on the expression of endothelial cell nitric oxide synthase (ecNODS) in conduit and resistance arteries. Aim #3 will determine the effect of HU on ecNOS mRNA content in conduit and resistance arteries. Aim #4 will determine the time course of the reductions in ecNOS activity and mRNA levels. Aim #5 will determine whether exposure to HU reduces vascular flow capacity and the potential for capillary exchange. It is hypothesized that endothelium-dependent vasodilation will be impaired in vessels isolated from rats exposed to HU.